Sorting signal targeting mRNA into hepatic extracellular vesicles

RNA Biol. 2014;11(7):836-44. doi: 10.4161/rna.29305. Epub 2014 Jun 12.

Abstract

Intercellular communication mediated by extracellular vesicles has proved to play an important role in normal and pathological scenarios. However not too much information about the sorting mechanisms involved in loading the vesicles is available. Recently, our group has characterized the mRNA content of vesicles released by hepatic cellular systems, showing that a set of transcripts was particularly enriched in the vesicles in comparison with their intracellular abundance. In the current work, based on in silico bioinformatics tools, we have mapped a novel sequence of 12 nucleotides C[TA]G[GC][AGT]G[CT]C[AT]GG[GA], which is significantly enriched in the set of mRNAs that accumulate in extracellular vesicles. By including a 3'-UTR containing this sequence in a luciferase mRNA reporter, we have shown that in a hepatic cellular system this reporter mRNA was incorporated into extracellular vesicles. This study identifies a sorting signal in mRNAs that is involved in their enrichment in EVs, within a hepatic non-tumoral cellular model.

Keywords: extracellular vesicles; mRNA; sorting signal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Cell Communication
  • Cell Line
  • Computational Biology / methods*
  • Gene Expression Profiling
  • Humans
  • Liver / cytology
  • Liver / metabolism*
  • Nucleic Acid Conformation
  • Nucleotide Motifs*
  • RNA Transport*
  • RNA, Messenger / chemistry*
  • RNA, Messenger / metabolism
  • Transport Vesicles

Substances

  • 3' Untranslated Regions
  • RNA, Messenger